Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

Brief Title

Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation

Official Title

Very Low-dose Total Body Irradiation in Combination With Total Lymphoid Irradiation and Anti-Thymocyte Globulin to Improve Donor Engraftment in Patients Undergoing Non-Myeloablative Hematopoietic Cell Transplantation

Brief Summary

      The purpose of this study is to evaluate whether addition of a low dose of total body
      irradiation (TBI) to a standard preparation for transplant [total lymphoid irradiation (TLI)
      and anti-thymocyte globulin (ATG)] conditioning will help to augment donor chimerism without
      reducing tolerability of this regimen or increasing the risk of graft-vs-host disease (GVHD)
    

Detailed Description

      Primary Objective:

      • Determine the proportion of patients with full donor T-cell chimerism at Day 28 following
      hematopoietic cell transplantation.

      Secondary Objectives:

        -  Determine the risk of disease progression, overall and event free survival, and
           non-relapse mortality, following treatment with TLI; ATG; and TBI.

        -  Determine the incidence of acute and chronic GVHD following treatment with TLI; ATG; and
           TBI.

      Exploratory Objectives:

      • Determine the changes in frequency of hematopoietic stem, progenitor, and mature cell
      subsets and the changes in cytokine milieu and cellular architecture in the bone marrow of
      patients receiving TLI compared to TLI+TBI.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Full-dose Donor Chimerism (FDC) at Day 28 Following TLI/ATG/TBI Conditioning.

Secondary Outcome

 Disease Progression

Condition

Acute Myeloid Leukemia

Intervention

Total body irradiation (TBI)

Study Arms / Comparison Groups

 TBI+TLI

Description:  TBI, single exposure on Day -1, 80 centigray (cGy) in addition to total lymphoid irradiation (TLI, 120 cGy/day for 9 days, weekends excluded) and anti-thymocyte globulin (ATG) 1.5 mg/kg (conditioning regimen)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Radiation

Estimated Enrollment

22

Start Date

November 5, 2018

Completion Date

November 17, 2020

Primary Completion Date

December 26, 2019

Eligibility Criteria

        INCLUSION CRITERIA

          -  Has a human leukocyte antigen (HLA)-matched or single allele mismatched adult sibling
             donor or unrelated donor.

          -  Acute myeloid leukemia (AML); myelodysplastic syndrome (MDS); myeloproliferative
             disease syndrome (MPD)]; chronic lymphocytic leukemia (CLL); B- or T-cell non Hodgkin
             lymphoma (NHL); Hodgkin lymphoma (HL); or chronic myelomonocytic leukemia (CMML),
             suitable for treatment with allogeneic transplant after TLI and ATG reduced intensity
             conditioning.

          -  Considered at high-risk for regimen-related toxicity from fully-ablative transplant
             conditioning (therefore reduced-intensity conditioning is recommended).

          -  Ability to understand and the willingness to sign a written informed consent document.
             Patients must have signed informed consent to participate in the trial.

        EXCLUSION CRITERIA

          -  Uncontrolled bacterial, viral or fungal infection defined as currently taking
             medication and progression of clinical symptoms.

          -  Progressive hemato lymphoid malignancy despite conventional therapy.

          -  Chronic myelogenous leukemia (CML).

          -  Active CNS involvement of the underlying malignancy.

          -  HIV positive

          -  Pregnant or lactating

          -  Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR
             treated ≤ 5 years ago but have a greater than 50% chance of life expectancy of ≥ 5
             years for that malignancy).

          -  Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of
             the primary physician would place the patient at an unacceptable risk from transplant.

          -  Left ventricular ejection fraction (LEVF) < 30%, or uncontrolled cardiac failure

          -  Diffusing capacity of lung for carbon monoxide (DLCO) < 40% predicted

          -  Total bilirubin > 3 mg/dL

          -  Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase
             (SGPT) > 4 x upper limit of normal (ULN)

          -  Creatinine > 2 mg/dL and an estimated creatinine clearance < 40 mL/min

          -  Poorly-controlled hypertension despite multiple antihypertensive medications

          -  Karnofsky Performance Status (KPS) < 60%
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Robert Lowsky, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT03734601

Organization ID

IRB-47407

Secondary IDs

BMT330

Responsible Party

Principal Investigator

Study Sponsor

Stanford University

Study Sponsor

Robert Lowsky, MD, Principal Investigator, Stanford University

Verification Date

May 2021